CPNE4

Chr 3

copine 4

Also known as: COPN4, CPN4

NCBI Gene: 131034 ENSG00000196353 UniProt: Q96A23 OMIM: 604208

This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.086

Z-score 3.78

OE 0.26 (0.15–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.65Z-score

OE missense 0.58 (0.51–0.66)

184 obs / 316.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.15–0.47)

0≤0.351.4

Missense OE?0.58 (0.51–0.66)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 30.5Missense obs/exp: 184 / 316.6Syn Z: -0.50

Background carrier burden — how many people carry a rare variant somewhere in CPNE4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

520 rare PASS variants

Rare truncating (LoF)

1 in 6,500

55 rare PASS variants

Rare synonymous (reference)

1 in 170

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPNE4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 7,700
South Asian	~43k	1 in 210	1 in 1,700
Remaining (unassigned)	~30k	1 in 240	≈ 1 in 15,000
European (Finnish)	~27k	1 in 220	≈ 1 in 13,000
Admixed American	~22k	1 in 140	≈ 1 in 5,600
African / African American	~21k	1 in 190	≈ 1 in 6,000
East Asian	~20k	1 in 160	1 in 3,300
Ashkenazi Jewish	~13k	1 in 710	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 260	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 15.? see exons ↓